2. Academic Validation
  3. Spatial proteomics identifies a CRTC-dependent viral signaling pathway that stimulates production of interleukin-11

Spatial proteomics identifies a CRTC-dependent viral signaling pathway that stimulates production of interleukin-11

  • Cell Rep. 2025 Feb 25;44(2):115263. doi: 10.1016/j.celrep.2025.115263.
Benjamin J Ravenhill 1,  Marisa Oliveira 1,  George Wood 2,  Ying Di 1,  Joanne Kite 1,  Xinyue Wang 1,  Colin T R Davies 1,  Yongxu Lu 3,  Robin Antrobus 1,  Gill Elliott 4,  Nerea Irigoyen 2,  David J Hughes 5,  Paul A Lyons 6,  Betty Chung 2,  Georg H H Borner 7,  Michael P Weekes 8
Affiliations

Affiliations

  • 1 Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK.
  • 2 Department of Pathology, University of Cambridge, Cambridge, UK.
  • 3 Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
  • 4 Department of Microbial Sciences, School of Biosciences, University of Surrey, Guildford, UK.
  • 5 School of Biology, University of St. Andrews, St. Andrews, UK.
  • 6 Department of Medicine, University of Cambridge, Cambridge, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
  • 7 Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried, Germany.
  • 8 Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK. Electronic address: mpw1001@cam.ac.uk.
PMID: 39921859 DOI: 10.1016/j.celrep.2025.115263
Abstract

Appropriate cellular recognition of viruses is essential for the generation of an effective innate and adaptive immune response. Viral sensors and their downstream signaling components thus provide a crucial first line of host defense. Many of them exhibit subcellular relocalization upon activation, resulting in the expression of interferon and Antiviral genes. To comprehensively identify signaling factors, we analyzed protein relocalization on a global scale during viral Infection. cAMP-responsive element-binding protein (CREB)-regulated transcription coactivators 2 and 3 (CRTC2/3) exhibited early cytoplasmic-to-nuclear translocation upon Infection with multiple viruses in diverse cell types. This movement was dependent on mitochondrial Antiviral signaling protein (MAVS), cyclo-oxygenase proteins, and protein kinase A. A key effect of CRTC2/3 translocation is transcription of the fibro-inflammatory cytokine interleukin (IL)-11. This may be important clinically in viral infections associated with fibrosis, including SARS-CoV-2. Nuclear translocation of CRTC2/3 is, therefore, identified as an important pathway in the context of viral Infection.

Keywords

CP: Cell biology; CP: Microbiology; CRTC; Sendai virus; interleukin-11; proteomics; systems virology; virus signaling.

Figures
Products